title: 2-Trifluoroacetylthiophene oxadiazoles as potent and selective class II human histone deacetylase inhibitors.
abstract: Trifluoroacetylthiophene carboxamides have recently been reported to be class II HDAC inhibitors, with moderate selectivity. Exploration of replacements for the carboxamide with bioisosteric pentatomic heteroaromatic like 1,3,4-oxadiazoles, 1,2,4-oxadiazoles and 1,3-thiazoles, led to the discovery that 2-trifluoroacetylthiophene 1,3,4-oxadiazole derivatives are very potent low nanomolar HDAC4 inhibitors, highly selective over class I HDACs (HDAC 1 and 3), and moderately stable in HCT116 cell culture.
authors.affiliation: IRBM-Merck Research Laboratories Rome, Via Pontina km 30,600-Pomezia, 00040 Rome, Italy. ester_muraglia@merck.com
authors.forename: Ester
authors.initials: E
authors.lastname: Muraglia
authors.forename: Sergio
authors.initials: S
authors.lastname: Altamura
authors.forename: Danila
authors.initials: D
authors.lastname: Branca
authors.forename: Ottavia
authors.initials: O
authors.lastname: Cecchetti
authors.forename: Federica
authors.initials: F
authors.lastname: Ferrigno
authors.forename: Maria Vittoria
authors.initials: MV
authors.lastname: Orsale
authors.forename: Maria Cecilia
authors.initials: MC
authors.lastname: Palumbi
authors.forename: Michael
authors.initials: M
authors.lastname: Rowley
authors.forename: Rita
authors.initials: R
authors.lastname: Scarpelli
authors.forename: Christian
authors.initials: C
authors.lastname: Steinkühler
authors.forename: Philip
authors.initials: P
authors.lastname: Jones
mesh_terms: D020650:Combinatorial Chemistry Techniques; D015195:Drug Design; D045325:HCT116 Cells; D051548:Histone Acetyltransferases / Q000037:antagonists & inhibitors; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000145:classification; D006801:Humans; D015394:Molecular Structure; D010069:Oxadiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D056572:Histone Deacetylase Inhibitors; D010069:Oxadiazoles; D013876:Thiophenes; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases